Metastatic or unresectable disease is the direct or indirect cause of 90% of all cancer deaths, and curative therapies for the treatment of metastatic cancers are rare. My ultimate goal is to develop methods that that enable us to achieve systemic tumor control after localized irradiation, when localized radiation therapy is indicated. There are no broadly effective systemic therapies for the treatment of metastatic soft tissue sarcomas, but localized palliative radiation therapy is commonly used and provides a therapeutic opportunity if an anti-tumor immune response is induced by immunotherapies administered at the time of the palliative radiation. Combining radiation with immunotherapy is a promising method for treating metastatic malignancies, and we hypothesized that the effects of radiation (RT) on immune cells in the tumor microenvironment will determine the utility of different immunotherapeutic (IT) methods in RT + IT combination therapies. We are identifying immunotherapies that combine effectively with radiation to promote systemic immune-mediated regression of metastatic disease.